LABORATORY FREEZE DRYERS ADVANCED PROCESSES

LABORATORY FREEZE DRYERS ADVANCED PROCESSES

IMA LIFE FREEZE DRYING SOLUTIONS. THE BEST IN FREEZE DRYING TECHNOLOGY THE BEST IN FREEZE DRYING TECHNOLOGY LABORATORY FREEZE DRYERS 6 UNCOMPROMISING PROCESS CONTROL 8 SUCCESSFUL OPTIMIZATION 9 LYOPHILIZATION PROCESS CONTROL 10 DRYING PROCEDURES FOR LABORATORY SYSTEMS 11 ALPHA 1- / - CONFIGURATIONS 1 GAMMA 1-16 / -16 CONFIGURATIONS 1 DELTA 1- / - CONFIGURATIONS 16 EPSILON 1- / - & 1-6D / -6D CONFIGURATIONS 17 TECHNICAL DATA 18

THE BEST IN FREEZE DRYING TECHNOLOGY HIGHEST LEVEL OF PROCESS-CONTROL AND REPRODUCIBILITY FOR RAPID, SAFE FREEZE DRYING OF YOUR HIGH-QUALITY PRODUCT. IMA Life supplies not only routine-process freeze dryers, but also a series of product-specific, highly specialized freeze dryers with far reaching potential. This line of equipment is distinguished by its innovative Lyo-Screen-Control (LSC) interface, its exceptional design and the most advanced level of refrigeration and vacuum technology. The freeze dryers are available with cylindrical drying chambers and, in the Epsilon range, with rectangular cross-section drying chambers. A practical and diverse collection of accessories permits a wide range of tasks. OUTSTANDING PRODUCTS, SUPERIOR TECHNOLOGY AND FULL CUSTOMER SUPPORT. Applying advanced processes to valuable products requires specific system configuration. We offer extensive advice in selecting a system and, on request, will run a freeze-drying test in our applications laboratory. IMA Life s high-quality freeze dryers are equipped with a modern, intuitive interface known as the Lyo-Screen-Control (LSC). It allows for up to 30 different drying programs with even the smallest machine as well as for the connection to a PC for process documentation and process control (pages 8, 9, 10).

YOUR VALUABLE PRODUCTS DEMAND THE BEST IN SPECIFIC SYSTEMS AND PROCESS MONITORING. Freeze dryers are increasingly being used for small batches whose production involves detailed information to create validation documents (IQ/OQ documentation) and to prepare monitoring tools that ensure flawless product quality. We not only use standard measurements of product temperature and pressure, but also measurements of electrical resistance (Lyocontrol, page 9) and weight-change (weighing cell, page 9) during the drying process. Optimal product safety can thus be guaranteed. Unacceptable structural changes including the collapse of the matrix, i.e. possible cross-contamination during the drying phase, can be avoided with confidence. 5

LABORATORY FREEZE DRYERS The optimal system for advanced applications: compact, high-performance laboratory and technical equipment requiring minimal space modular systems permit capacity expansion with a wide variety of accessories complete processing of entire freezedrying cycle in ice condenser chamber, program controlled, if desired, from -30 C (prefreezing) with single-stage compressors, to -50 C (prefreezing) with doublestage compressors innovative, easy-to-use interface LSC with PC connection for process control and documentation freeze-dryer system fulfills FDA and cgmp-guidelines, interface fulfills the current requirements according to GAMP, Lyo-software LPC-16 also meets US CFR requirements drying chamber is located directly above the ice condenser chamber; maximum cross-sectional area results in high sublimation performance and shortest possible process-time ice condenser chamber with inner condenser coil of high quality steel allows for effi cient vapour deposition thermal insulation of ice condenser chamber avoids power loss and eliminates build-up of water condensation Ice condenser can be checked visually easily accessible ice condenser; rapid, easy defrosting and cleaning (electrical or hotgas defrosting available); mechanical or electric defrosting drain chemically resistant systems for freeze drying solvents (e.g. DMSO, Acetonitrile, Tert-Butanol, Dioxane) are available Windows-based software LPC-16 (Lyophilization Process Control) for PC process control and documentation available with all systems simple alternative process documentation using IMA Life printer or Lyolog LL-1 software when required, system qualification (IQ/OQ documentation) for validation purposes Alpha 1- / - Gamma 1-16 / -16 Delta 1- / - 6

The Epsilon 1- / - and Epsilon 1-6 D / -6 D set the standard for systems of the highest quality and performance. They share a geometrical likeness with large production machines and use similar temperaturecontrolling systems. The Epsilon 1- / - units have an ice condenser temperature with a minimum of -55 C and -85 C respectively and is available with one shelf with 0.11 m usable surface area. The pictures on page 17 show the variety of applications to the freeze drying of products in bulk or vials. The anodized Aluminium shelves can be directly heated or cooled, making the Epsilon 1- / - suitable for both experimental and routine freeze drying. The two larger models, Epsilon 1-6 D and -6 D, are characterized by their drying potential on a maximum of four shelves with an area of 0.8 m, their distance between shelves can reach 75mm (with three shelves). Due to the temperature control of the stainless steel shelves (via a synthetic heat-transfer medium), these systems fulfill the highest standards of the pharmaceutical and biotech industries. New cooling techniques allow for shelf temperatures of -0 C and -55 C/-70 C (prefreezing) in the very compact chambers of the Epsilon 1- and 1-6 D and the Epsilon - and -6 D, respectively. This permits extremely sensitive pharmaceutical and biotech products, e.g. amorphous structures with a low glass transition point, to be freeze dried safely. These Epsilon dryers are also available with liquid nitrogen cooling. Simple, process-specific documentation is possible on all systems as a result of the new Lyo-Screen- Control and Lyolog interface. The innovative weighing cell provides the ability to monitor freeze drying in vials and trays, in addition to the standard measurements of product temperature and pressure. An added option is the Windows-based LPC-16 software for PC process control and documentation. LPC-16 follows the GAMP and cgmp guidelines. Other cgmp guidelines are also followed including maintenance and surface guidelines. The systems can be H O sterilized and can be delivered with an Installation/Operation qualification. All systems are very flexible; all are available with manual stoppering devices and additional manifolds for lyophilization in round bottom flasks. These systems will contribute to the success of your small batch production and product development. THE HIGHEST LEVEL OF RESEARCH AND DEVELOPMENT FOR NEW PRODUCTS Epsilon 1- / - Epsilon 1-6 D / -6 D 7

UNCOMPROMISING PROCESS CONTROL The users of laboratory freeze dryers increasingly demand the highperformance process control that is an integral part of commercial freeze drying in the high-tech industries. A recent development is the LSC (Lyo-Screen-Control). This intuitive, simple to control interface has the following attributes: 1/ VGA-LC-DISPLAY GRAPHIC USER INTERFACE WITH TURN AND PUSH ONE-BUTTON INTERFACE CLEAR OVERVIEW OF IMPORTANT PROCESS DATA UP TO 30 FREEZE DRYING PROGRAMS CAN BE ENTERED IN TABULAR FORM (OPTIONAL) RECORDING OF PROCESS DATA USING DOCUMENTATION LYOLOG LL-1 SOFTWARE (OPTIONAL) SCADA-SYSTEM LPC-16 AVAILABLE AS WINDOWS SOFTWARE (OPTIONAL) Table of values Table for conversion of vacuum/product temperature The ease in recording product-specific drying profiles on a PC is greatly improved and can simulate conditions on large production systems (process optimization, scale up). Program-creation module PGM-30 LSC-Controller with system diagram Program-editing window 8

SUCCESSFUL OPTIMIZATION WEIGHING SYSTEM CWS-0: DETERMINING THE SPEED AND END OF A FREEZE- DRYING PROCESS The weighing system is an innovative online monitor of freeze drying in vials or in trays (bulk ware). It is used in addition to the traditional measuring of product temperature and electrical resistance. the weighing cell, able to function in a vacuum and under extreme temperature changes, remains in the freeze dryer throughout the process the sample remains in its place, next to the other flasks on the shelf, insuring accurate results continual measurements allow for determining drying speeds during the process easy recognition, through weight loss, of the end of drying process online recording of measurement results using Windows based software primarily used in pilot freeze dryers LYOCONTROL LC-1 The freezing range of a substance can be determined with the Lyocontrol measuring system. The measured readings, product temperature, and electrical resistance provide information about the product s reaction to freeze drying, allowing a safe set of parameters to be determined for the process. The direct integration of data into the automatic process control is possible. DOCUMENTATION SOFTWARE LYOLOG LL-1 Freeze dryers with the LSC interface system can be directly connected to external hardware including PC s and printers. Our Lyolog LL-1 documentation software allows for direct and precise documentation of batch data and process results. 9

LYOPHILIZATION PROCESS CONTROL The LPC-16 visual processing and interface is for the use, supervision and documentation of the freeze-drying process. The LPC-16 complies with the relevant GAMP and CFR guidelines. The LPC-16 is compatible with different PC software and customized hardware components (e.g. LSC, Siemens-SPS) for individual process control. Important features include: SIMPLE TO USE INTERFACE GRAPHICAL DISPLAY OF SYSTEM S CURRENT POSITION FREE SELECTION OF MEASUREMENT VALUES TO BE GRAPHICALLY DISPLAYED, ZOOM FUNCTION TABLE WITH ALL PROCESS EVENTS GRAPHIC SUPPORT FOR PROCESS PROGRAMMING (RECIPE) INPUT OF BATCH-RELATED INFORMATION ARCHIVE AND PROCESS DOCUMENTATION INCLUDING DATA EXPORT (E.G., INTO EXCEL) PLAUSIBILITY CONTROL AND USER-CODE CHECKS AT DATA ENTRY SYSTEM SECURITY DUE TO DIFFERENT ACCESS LEVELS OPTIMAL INTEGRITY OF DATA THROUGH USE OF BINARY FORMATS THAT CAN NOT BE MANIPULATED RECORDING OF SINGLE ASSIGNED PROCESS FILE (AUDIT TRAIL) DATA STORAGE THROUGH NETWORKS OR ON PORTABLE MEDIA Display of system status Program creation Process documentation 10

DRYING PROCEDURES FOR LABORATORY SYSTEMS The freeze dryers with LSC controllers set new standards for flexibility and process control. The varied, modular accessory line allows for individual system configurations adaptable to almost all freeze-drying demands. Two different drying techniques provide a solution to most lyophilization challenges: PROCESS A (SINGLE-CHAMBER SYSTEM) Freezing and careful drying of low-freezing, thermally-unstable substances, on cooled shelves (up to -0C) inside the ice condenser chamber. Types of vessels used: dishes injection-vials (stoppering under vacuum) SHELF CAPACITY ALPHA GAMMA DELTA Shelf with ø 00 mm 1 5 10 Shelf with ø 00 mm and stoppering device 1 - - PROCESS B (DOUBLE-CHAMBER SYSTEM) Separate freezing (e.g. using a freezer) and drying outside the ice condenser chamber. Types of vessels used: dishes injection-vials (stoppering under vacuum) round bottom flasks, wide-neck filter bottles (max. 1 and connections with acrylic glass drying chamber or stainless steel manifold) ampoules (connected to special distributors or stainless steel manifold) SHELF CAPACITY ALPHA GAMMA DELTA Shelf with ø 00 mm, max. 5/10 5/10 5/10 Shelf with ø 375 mm, max. 5 8 8 Shelf with ø 50 mm and stoppering device, max. - Shelf with ø 50 mm and stoppering device, max. / / / 11

ALPHA 1- / - CONFIGURATIONS SYSTEM SELECTION Incremental condensing performance for every application. In addition to selecting the accessories, the following criteria should be taken into account when choosing a freeze-drying system: required ice condenser temperature (-55 C for water-based samples, -85 C for substances with low freezing points or containing solvents) number of shelves, i.e. number of flasks needed for the amount of product per batch maximum ice condenser performance required (kg/h) i.e. total quantity of ice produced until defrosted Configuration tailored to your procedural needs. The adjacent illustrations show examples of the range of system configurations; you can choose the models and accessories that fit your requirements. Do not hesitate to contact us for an individual configuration of your system. We will gladly provide assistance. 1 3 5 6 7 8 9 10 11 Freezing and drying inside ice condenser chamber (process A) on one temperature controlled shelf (ø 00 mm, total area = 0.031 m ) Freezing and drying inside ice condenser chamber (process A) on one temperature controlled shelf with stoppering device (ø 00 mm, total area = 0.031 m ) drying chambers with ports for flasks, wide-neck filter bottles or distributors for ampoules Manifold for 8 round bottom flasks, wide-neck filter bottles or distributors for ampoules, specially suited for the drying of solvents 5 heatable shelves (ø 00 mm, total area = 0.155 m, distance between shelves = 5 mm - can be varied by removing single shelves) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules 10 heatable shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) 10 heatable shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules heatable shelves with stoppering device (ø 50 mm, total area = 0.09 m, distance between shelves = 5 mm - can be increased to 110 mm by removing one shelf) additional ports for 1 round bottom flasks, wide -neck filter bottles or distributors for ampoules heatable shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 50 mm - can be varied by removing single shelves) 5 heatable shelves (ø 375 mm, total area = 0.55 m, distance between shelves = 67 mm - made possible with special adapter plate) 1 drying chamber with additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules, additional connection to a rotation vacuum concentrator (e.g. RVC -5) available 1

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GAMMA 1-16 / -16 CONFIGURATIONS 1 3 5 6 7 8 9 Freezing and drying inside ice condenser chamber (process A) on 5 temperature controlled shelves (ø 00 mm, total area =0.155 m, distance between shelves = 5 mm - can be varied by removing single shelves) Freezing and drying inside ice condenser chamber (process A) on temperature controlled shelves with stoppering device (ø 50 mm, total area = 0.09 m, distance between shelves = 5 mm - can be increased to 110 mm by removing 1 shelf) drying chambers with ports for flasks, wide-neck filter bottles or distributors for ampoules Manifold for round bottom flasks, wide-neck filter bottles or distributors for ampoules, specially suited for the drying of solvents 5 heatable shelves (ø 00 mm, total area = 0.155 m, distance between shelves 5 mm - can be varied by removing single shelves) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules 10 heatable shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) heatable shelves with stoppering device (ø 50 mm, total area = 0.09 m, distance between shelves = 5 mm can be increased to 110 mm by removing 1 shelf) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules heatable shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 50 mm - can be varied by removing single shelves) heatable shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 50 mm - can be varied by removing single shelves) 8 heatable shelves (ø 375 mm, total area = 0.88 m, distance between shelves = 8 mm - larger distances can be obtained by special order) 1

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DELTA 1- / - CONFIGURATIONS 1 3 Freezing and drying inside ice condenser chamber (process A) on 10 temperature controlled shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) Freezing and drying inside ice condenser chamber (process A) on temperature controlled shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 5 mm - can be increased to 110 mm by removing one shelf) drying chambers with ports for flasks, wide-neck filter bottles or distributors for ampoules 5 6 10 heatable shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules heatable shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 50 mm - can be varied by removing single shelves) additional ports for 1 round bottom flasks, wide-neck filter bottles or distributors for ampoules 8 heatable shelves (ø 375 mm, total area = 0.88 m, distance between shelves = 8 mm - larger distances can be obtained by special order) 1 3 5 6 16

EPSILON 1- / - & 1-6D / -6D CONFIGURATIONS A variety of Epsilon 1- / - configurations are possible due to a very clever and variable system of shelves that serve as an intermediate valve and defrosting plate for the ice condenser. A selection of these combinations isillustrated here. 1 3 Freezing and drying inside ice condenser chamber (process A) on 10 temperature controlled shelves (ø 00 mm, total area = 0.31 m, distance between shelves = 5 mm - can be varied by removing single shelves) Freezing and drying inside ice condenser chamber (process A) on temperature controlled shelves with stoppering device (ø 50 mm, total area = 0.18 m, distance between shelves = 5 mm - can be increased to 110 mm by removing one shelf) drying chambers with ports for flasks, wide-neck filter bottles or distributors for ampoules 1 3 CONFIGURATIONS EPSILON1-6 D / -6 D While the shelves in the Epsilon 1- / - are cooled directly by the coils of the cooling system; the temperature regulation in the bigger 6 kg model is achieved indirectly through a highperformance, synthetic heat-transfer medium. This guarantees minimum temperature variation at any point on the shelves, less than +/-1K, and requires an identical amount of overall energy for the lyophilization. Manipulator for retrieving individual vials during freeze-drying process (sample thief) 17

TECHNICAL DATA ALPHA 1- ALPHA - GAMMA 1-16 GAMMA -16 DELTA 1- DELTA - Ice condenser capacity: - capacity (max. kg) - performance (max. kg/h) - temperature (approx.c) ca. -60 ca. -85 16 1 ca. -60 16 1 ca. -85 18 ca. -55 18 ca. -85 Shelf temperature (T in C) when freezing inside ice condenser chamber ca. -30 ca. -0 ca. -0 ca. -55 ca. -0 ca. -55 Max. shelf surface area when drying inside the ice condenser chamber (process A) 1 shelf ø=00 mm, ^= 0.031 m 1 shelf ø=00 mm, ^= 0.031 m 5 shelf ø=00 mm, ^= 0.155 m 5 shelf ø=00 mm, ^= 0.155 m 10 shelf ø=00 mm, ^= 0.31 m 10 shelf ø=00 mm, ^= 0.31 m Max. shelf surface area when drying inside the ice condenser chamber in injection vials with stoppering under vacuum or inert gas (process A) 1 shelf ø=00 mm, ^= 0.031 m 1 shelf ø=00 mm, ^= 0.031 m shelf ø=50 mm, ^= 0.09 m shelf ø=50 mm, ^= 0.09 m shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m Max. shelf surface area when drying outside the ice condenser chamber (process B) 5 shelf ø=375 mm, ^= 0.55 m 5 shelf ø=375 mm, ^= 0.55 m 8 shelf ø=375 mm, ^= 0.88 m 8 shelf ø=375 mm, ^= 0.88 m 8 shelf ø=375 mm, ^= 0.88 m 8 shelf ø=375 mm, ^= 0.88 m Max. shelf surface area when drying outside the ice condenser chamber in injection vials with stoppering under vacuum or inert gas (process B) shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m shelf ø=50 mm, ^= 0.18 m Drying in round bottom flasks or wide-neck filter bottles 1/ pieces 1/ pieces 1/ pieces 1/ pieces 1//36 pieces 1//36 pieces Dimensions of base unit width: 390 mm height: 15 mm depth: 555 mm width: 390 mm height: 15 mm depth: 555 mm width: 860 mm height: 85 mm depth: 650 mm width: 860 mm height: 85 mm depth: 650 mm width: 860 mm height: 1050 mm depth: 650 mm width: 860 mm height: 1050 mm depth: 650 mm Weight ca. 8 kg ca. 60 kg ca. 135 kg ca. 160 kg ca. 15 kg ca. 50 kg Electrical connection (other voltages available) 30 V, 50 60 Hz 30 V, 50 60 Hz 30 V, 50 60 Hz 30 V, 50 60 Hz 00 V, 50 60 Hz 00 V, 50 60 Hz Max. power consumption ca. 1.6 kva ca. 1.8 kva ca..1 kva ca..3 kva ca. 1.8 kva ca. 3.0 kva Max. ambient temperature (unit is aircooled, higher temperatures upon request) climate category SN+10C to +5C climate category SN+10C to +5C climate category SN+10C to +5C climate category SN+10C to +5C climate category SN+10C to +5C climate category SN+10C to +5C We reserve the right to make technical changes without prior notice. 18

EPSILON 1- EPSILON - EPSILON 1-6 D EPSILON -6 D Ice condenser capacity - capacity (max. kg) - performance (max. kg/h) - temperature (approx.c) -55-85 6-55 6-85 Shelf temperature (T in C) -0 (prefreezing) to +60-70 (prefreezing) to +60-0 (prefreezing) to +60-50 (prefreezing) to +60 Shelves - quantity Shelf measurements (w x d, mm) Area (m ) Distance between shelves (mm) 1 70 x 00 0.11 135 1 70 x 00 0.11 135 +1 max. 5 x 300 0.07-0.8 73 mm (3+1) +1 max. 5 x 300 0.07-0.8 73 mm (3+1) Sealing of vials in vacuum / N Flask drying Manifold with e.g. controllable vacuum connections each (optional) Manifold with e.g. 8 controllable vacuum connections each (optional) Sterilization (H O ) Refrigeration compressor Number x KW 1 x 0.6 x 0.6 1 x 0.6 +1 x 0.5 1 x 0.5 + x 0.6 Type air-cooled air-cooled air-cooled air-cooled Dimensions (w x d x h, mm) Electrical connection (V /Hz / kva) Weight (kg) 780x80x ca.50 30/50/3 ca. 175 780x80x ca.50 30/50/3 ca. 05 860x650x ca.1100 30/50/3 ca. 310 860x650x ca.1100 30/50/3 ca. 310 Interface LSC LSC LSC LSC Vacuum display Vacuum control function Temperature display: - Ice condenser (display) - Shelves (display and control) - product (measurement of 3 probes max.) Lyo Control Determining end of drying: - Product temperature measurement - Pressure-increase measurement Weighing cell Manipulator for sample-retrieval during process Programmer module PC-Interface PC-Documentations software Lyo LL-1 Process-control system LPC-16 = optional = standard We reserve the right to make technical changes without prior notice. 19

www.ima.it IMA LIFE reserves the right to make any changes to the described machine characteristics. April 010-991EAD001 IMA LIFE North America Inc. 175 Military Road, Tonawanda - New York 1150 - United States of America Tel. +1 716 695 635 - Fax +1 716 695 6367 sales@imalife.com - services@imalife.com 0